ABSTRACT
Adrenoleukodystrophy (ALD) is a progressive cerebral degenerative disorder with onset in childhood, in which there is increased pigmentation of the skin and laboratory evidence of degenerative disease of the adrenal. The specific biochemical abnormality in ALD is the accumulation of very long-chain unbranched fatty acids, which are saturated or mono-unsaturated. The gene for ALD was found by positional cloning within the Xq28 region. The course of ALD has usually been relentless, and no therapeutic measures appear to be effective. By analogy with its beneficial effect in sickle cell anemia, where they increase fetal hemoglobin, butyrate and 4-phenylbutyrate have been explored in ALD. Cultured cells from patients were found to have improvement in the oxidation of very long-chain fatty acids (VLCFA), and amounts of stored VLCFA in the brain of a mouse model were decreased by exposure to phenylbutyrate. Preliminary studies in man are said to be underway.
